This invention relates to a new and safe therapy involving coenzyme Q.sub.10 for human subjects who have retrovirus-related diseases such as Acquired Immune Deficiency Syndrome (AIDS) and the AIDS-Related Complex (ARC).
The direct or indirect causes of AIDS and other diseases including ARC, are now known to be certain retroviruses. The third human retrovirus to be identified is described as the human T-lymphotropic virus III (HTLV-III) and is also known as human immunodeficiency virus (HIV). A retrovirus is a virus having RNA as its primary genetic entity.
Mechanistically, T.sub.4 helper-inducer lymphocytes appear to become infected with HIV. Normally, a single uninfected T.sub.4 lymphocyte may proliferate to yield 1000 or more progeny. When a T.sub.4 lymphocyte is infected with HIV, as few as 10 cells may result from such a proliferation. Infection with this virus results in a profound depletion of the T.sub.4 lymphocyte population.
Patients with AIDS may develop a variety of threatening or lethal ancillary conditions such as pneumonia or Kaposi's sarcoma. This sarcoma is a tumor of blood vessel tissue in the skin or internal organs. The advent of AIDS and ARC has been viewed as a--"modern plague"--which has already killed an astounding number of people. Consequently, prophylactic treatment of uninfected individuals and therapy of patients afflicted with these retrovirus diseases have the highest priority.
Vaccination is one approach to therapy, but the task of producing an effective vaccine is particularly difficult because AIDS-related viruses have great genetic variability. This variability is the basis of a continuum of related retrovirus strains. An effective vaccine for widespread clinical use is not expected to soon be available.
Presently, the drugs or synthetic medicinals most commonly being tested as a treatment for AIDS are inhibitors of the unique retroviral enzyme, reverse transcriptase. Some of these are chemical analogues of nucleosides that form the subunits of DNA. One such drug is azidothymidine (AZT). This drug is known to have some toxicity and may suppress proliferation of bone marrow cells. Such effects may limit the use of AZT for the long periods of time likely to be necessary to control retroviral diseases.
One approach to the therapy or control of human retroviral disease is to resuscitate the depleted immune system of the patient. This approach has the potential to be effective despite the genetic variability of the retrovirus and to have important advantages over vaccines and classical medicinals.
The human immune system is complex and incompletely understood. No therapeutic approach has heretofore been established to improve the immune system in a manner enabling the control of retroviral disease. There are at least two general approaches for stimulation of the immune system by biochemical mechanisms. One such approach would be to use immune stimulants which are foreign to the human body and which may be categorized as nonspecific adjuvant-type medicinals. A second approach would be to pursue activation of intrinsic mechanisms of the immune system by using substances normally present, for example, in human tissue. The latter approach has prospect of beneficially stimulating the immune system while minimizing or avoiding undesirable side effects.
A study of the biochemistry and the immunology of lymphocytes reveals a wide array of interaction. For example, T.sub.4 helper-inducer lymphocytes help plasma cells secrete antibody, induce maturation of T.sub.8 cytotoxic cells and suppress maturation of B cells. The T.sub.4 helper-inducer lymphocytes, under different circumstances, may induce maturation of B cells and proliferation of memory clones and induce T.sub.8 suppressor cells. The T.sub.8 suppressor cells in turn suppress differentiation to T.sub.8 cells via the participation of suppressor factor.
Bliznakov et al., administered CoQ.sub.10 to mice with tumors which had been induced by dibenzpyrene. They observed a resultant reduction of the percentage of mice with tumors, a reduction in the tumor size of those mice that developed tumors, and an increase in the number of survivors (Experientia, 26:953-954 (1970)). Bliznakov et al. used a parasitic model consisting of mice infected with Plasmodium berghei (a malarial organism) and found that the administration of CoQ.sub.10 potentiated the effectiveness of chloroquine, increased survivors, prolonged survival time, and reduced parasitemia in red blood cells. It was suggested by Bliznakov et al. that CoQ.sub.10 interacted in mechanisms of the immune system, but the specific nature of such interactions was unknown (Book of Abstracts, VI International Meeting of the Reticuloendothelial Society, Freiburg, Germany, p. 14 (1970); Bliznakov, In: The Reticuloendothelial System and Immune Phenomena, edited by DiLuzio, N. R., Plenum Press, N.Y., 315-322 (1971)).
Coenzyme Q.sub.10 (CoQ.sub.10) has been used for a variety of nutritional or medical purposes. CoQ.sub.10 (2,3-dimethoxy-5-methyl-6-decaprenyl benzoquinone) may be an important component of the mitochondrial metabolic system and be related to efficient function of the immune system. A method for controlling and/or reversing immunological senescence in animals by administering CoQ.sub.10 is described in U.S. Pat. No. 4,156,718. Coenzyme Q.sub.10 use for treatment of myasthenia was described in U.S. Pat. No. 4,068,003.
The present invention resulted, at least in part, from research described herein which was directed toward restoration of depleted immune systems of AIDS patients.